ATM/ATR

Signaling Pathway Map

Research Area

Inhibitory Selectivity

Isoform-specific Inhibitors

ATM/ATR Products

All (20) ATM/ATR Inhibitors (19) ATM/ATR Activators (1)

Catalog No.	Information	Product Use Citations	Product Validations
S1009	Dactolisib (BEZ235) Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell.	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 35(5):752-766 Cancer Cell, 2019, 36(2):179-193	Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.
S1092	KU-55933 (ATM Kinase Inhibitor) KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/K_i of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.	Nat Commun, 2020, 11(1):123 Cell, 2019, 178(2):361-373 Cancer Cell, 2019, 35(5):752-766	Effects of NVP-BKM120 and KU-55933 and their combination on the DNA damage response. A, HCC1937 cells were treated for 18 hours with NVP-BKM120 at 2.5 μmol/L, KU-55933 at 10 μmol/L, or their combination, subjected to ionizing radiation(IR) with 10 Gy or mock, lysed 6 hours later, and subjected to immunoblotting with antibodies as indicated.
S1570	KU-60019 KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.	Cell, 2019, 176(3):505-519 Nucleic Acids Res, 2019, 47(18):9467-9479 Nucleic Acids Res, 2019, 47(16):8838-8859
S8007	VE-821 VE-821 is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.	Nat Commun, 2020, 11(1):123 Am J Physiol Gastrointest Liver Physiol, 2020, 10.1152/ajpgi.00329.2019 Nature, 2019, 10.1038/s41586-019-1607-3	Western blot for γH2AX in H460 cells treated with Cr(VI) in the presence of a second set of inhibitors (ATM-i2—10 uM KU55933, DNAPK-i2—10 uM NU7441, ATR-i2—10 uM VE821). “γH2AX-total” numbers indicate a total normalized intensity of both γH2AX bands from 2 Western blots.
S2758	Wortmannin Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Also blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays.	Cell, 2019, 176(6):1379-1392 Nat Cell Biol, 2019, 21(2):226-237 Adv Sci (Weinh), 2019, 6(8):1801233	L3.6pl cells at 6,000 cells per well were incubated in MEM with 5% FBS in triplicate in a 96-well culture plate and then treated alone with 5 umol/L BMS-777607, 10 umol/L wortmannin, or with BMS-777607 in combination with individual inhibitors. Polyploidy was examined under BK71 Olympus microscope and photographed 72 hours after treatment.
S2817	Torin 2 Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively.	Nat Commun, 2020, 11(1):71 Cell Metab, 2019, 29(5):1166-1181 Nat Commun, 2019, 10(1):1444	U2OS cells were plated in six-well plates using complete medium. The next day the cells were washed four times with NaCl/P_i before maintaining them for 6 h in serum- and glucose-free DMEM supplemented as indicated in the absence or presence of 0.1 uM Torin 2 for the last 1 h. The cells were control- treated, treated with 1 ug/mL insulin or treated with 1 mM H2O2 for 15 min. Thereafter, cell lysates were prepared and western blotting was performed using the indicated antibodies.
S2245	CP-466722 CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells.	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 36(2):179-193 Mol Cells, 2019, 42(3):210-217
S7102	Berzosertib (VE-822) VE-822 is an ATR inhibitor with IC50 of 19 nM in HT29 cells.	Cell, 2019, 176(1-2):144-153 Mol Cell, 2019, 73(1):22-35.e6 Nat Commun, 2019, 10(1):5304	Western blot analysis of scr or siPNUTS transfected cells without IR or 6 h after 10 Gy. VE-822 was added for 2, 5, 15, 30 or 60 min to indicated samples 6 h after 10 Gy.
S8050	ETP-46464 ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM.	Nat Commun, 2019, 10(1):5718 Nat Commun, 2019, 10(1):3585 Oncogenesis, 2019, 8(7):38
S7136	CGK 733 CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM.	Mol Cells, 2016, 39(12):869-876	K562 and K562R cells were pre-treated for 1 h with CGK733 (5 μM), then treated with CTD (10 μM) for 24 h, and protein levels of cleaved PARP, Mcl-1, and phosphorylated H3 were determined by Western blotting. GAPDH served as a normal control.
S7050	AZ20 AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.	Cell, 2019, 176(3):505-519 Mol Cell, 2019, 10.1016/j.molcel.2019.09.024 Nucleic Acids Res, 2019, 10.1093/nar/gkz518	(B) SAHA treatment impairs the HR capacity of GBM03 cells. AZ20(ATRi) as a positive control.
S8556	AZ31 AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ).
S7693	AZD6738(Ceralasertib) AZD6738 is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.	Nature, 2019, 10.1038/s41586-019-1607-3 Nature, 2019, 574(7777):268-272 Mol Cell, 2019, 74(6):1123-1137	Number of γH2AX foci per cell of irradiated (2 Gy) SAS cells treated with inhibitors against ATM (ATMi, KU55933), DNA-PK (DNA-PKi, KU57788), or ATR (ATRi, AZD6738) with or without LY364947.
S8729	AZ32 AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.
S8680	AZD1390 AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.	Cell Death Differ, 2019, 10.1038/s41418-019-0393-7
S3600	Schisandrin B (Sch B) Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety.	Inflammation, 2017, 40(6):1903-1911
S8096	Mirin Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity.	Aging, 2018, 10(4):549-560 DNA Repair, 2018, 70:67-71 Mol Cell Biol, 2017, 37(20)	Wildtype bone marrow-derived macrophages (BMDMs) were incubated with and without the MRN complex inhibitor mirin (administered dose of 100 μM) for 2 hours, then were treated with PM (100 μg/mL) for an additional 24 hours. (A) The relative levels of Cxcl1, Cxcl2 and Ifn-γ mRNA transcripts were determined using quantitative PCR. (B) The protein levels of Cxcl1, Cxcl2 and Ifn-γ in the culture supernatants were measured using ELISA. Data are presented as means ± SEMs across at least 3 independent experiments. p < 0.05; *p < 0.01.
S8666	BAY 1895344 (BAY-1895344) BAY 1895344 is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM.	Nucleic Acids Res, 2019, 10.1093/nar/gkz518
S8375	AZD0156 AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities.	Mol Cell, 2019, 74(3):571-583 Oncogene, 2019, 38(14):2451-2463 Mol Cancer Ther, 2019, 10.1158/1535-7163.MCT-19-0474
S4157	Chloroquine diphosphate Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator.	Sci Adv, 2019, 5(10):eaax7142 EMBO Mol Med, 2019, 11(10):e9930 Theranostics, 2019, 9(26):8392-8408	NCI-H929 EV and miR-137 OE cells were treated with ATM activator Chloroquine Phosphate (CQ), specific ATM inhibitor KU-55933, and ATR inhibitor AZ20 for 12 hr. Immunoblotting showed the expression of p-ATM, p-Chk2, p-BRCA1, p-ATR and p-Chk1.

Catalog No.	Information	Product Use Citations	Product Validations
S1009	Dactolisib (BEZ235) Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell.	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 35(5):752-766 Cancer Cell, 2019, 36(2):179-193	Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.
S1092	KU-55933 (ATM Kinase Inhibitor) KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/K_i of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.	Nat Commun, 2020, 11(1):123 Cell, 2019, 178(2):361-373 Cancer Cell, 2019, 35(5):752-766	Effects of NVP-BKM120 and KU-55933 and their combination on the DNA damage response. A, HCC1937 cells were treated for 18 hours with NVP-BKM120 at 2.5 μmol/L, KU-55933 at 10 μmol/L, or their combination, subjected to ionizing radiation(IR) with 10 Gy or mock, lysed 6 hours later, and subjected to immunoblotting with antibodies as indicated.
S1570	KU-60019 KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.	Cell, 2019, 176(3):505-519 Nucleic Acids Res, 2019, 47(18):9467-9479 Nucleic Acids Res, 2019, 47(16):8838-8859
S8007	VE-821 VE-821 is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.	Nat Commun, 2020, 11(1):123 Am J Physiol Gastrointest Liver Physiol, 2020, 10.1152/ajpgi.00329.2019 Nature, 2019, 10.1038/s41586-019-1607-3	Western blot for γH2AX in H460 cells treated with Cr(VI) in the presence of a second set of inhibitors (ATM-i2—10 uM KU55933, DNAPK-i2—10 uM NU7441, ATR-i2—10 uM VE821). “γH2AX-total” numbers indicate a total normalized intensity of both γH2AX bands from 2 Western blots.
S2758	Wortmannin Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Also blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays.	Cell, 2019, 176(6):1379-1392 Nat Cell Biol, 2019, 21(2):226-237 Adv Sci (Weinh), 2019, 6(8):1801233	L3.6pl cells at 6,000 cells per well were incubated in MEM with 5% FBS in triplicate in a 96-well culture plate and then treated alone with 5 umol/L BMS-777607, 10 umol/L wortmannin, or with BMS-777607 in combination with individual inhibitors. Polyploidy was examined under BK71 Olympus microscope and photographed 72 hours after treatment.
S2817	Torin 2 Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively.	Nat Commun, 2020, 11(1):71 Cell Metab, 2019, 29(5):1166-1181 Nat Commun, 2019, 10(1):1444	U2OS cells were plated in six-well plates using complete medium. The next day the cells were washed four times with NaCl/P_i before maintaining them for 6 h in serum- and glucose-free DMEM supplemented as indicated in the absence or presence of 0.1 uM Torin 2 for the last 1 h. The cells were control- treated, treated with 1 ug/mL insulin or treated with 1 mM H2O2 for 15 min. Thereafter, cell lysates were prepared and western blotting was performed using the indicated antibodies.
S2245	CP-466722 CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells.	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 36(2):179-193 Mol Cells, 2019, 42(3):210-217
S7102	Berzosertib (VE-822) VE-822 is an ATR inhibitor with IC50 of 19 nM in HT29 cells.	Cell, 2019, 176(1-2):144-153 Mol Cell, 2019, 73(1):22-35.e6 Nat Commun, 2019, 10(1):5304	Western blot analysis of scr or siPNUTS transfected cells without IR or 6 h after 10 Gy. VE-822 was added for 2, 5, 15, 30 or 60 min to indicated samples 6 h after 10 Gy.
S8050	ETP-46464 ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM.	Nat Commun, 2019, 10(1):5718 Nat Commun, 2019, 10(1):3585 Oncogenesis, 2019, 8(7):38
S7136	CGK 733 CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM.	Mol Cells, 2016, 39(12):869-876	K562 and K562R cells were pre-treated for 1 h with CGK733 (5 μM), then treated with CTD (10 μM) for 24 h, and protein levels of cleaved PARP, Mcl-1, and phosphorylated H3 were determined by Western blotting. GAPDH served as a normal control.
S7050	AZ20 AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.	Cell, 2019, 176(3):505-519 Mol Cell, 2019, 10.1016/j.molcel.2019.09.024 Nucleic Acids Res, 2019, 10.1093/nar/gkz518	(B) SAHA treatment impairs the HR capacity of GBM03 cells. AZ20(ATRi) as a positive control.
S8556	AZ31 AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ).
S7693	AZD6738(Ceralasertib) AZD6738 is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.	Nature, 2019, 10.1038/s41586-019-1607-3 Nature, 2019, 574(7777):268-272 Mol Cell, 2019, 74(6):1123-1137	Number of γH2AX foci per cell of irradiated (2 Gy) SAS cells treated with inhibitors against ATM (ATMi, KU55933), DNA-PK (DNA-PKi, KU57788), or ATR (ATRi, AZD6738) with or without LY364947.
S8729	AZ32 AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.
S8680	AZD1390 AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.	Cell Death Differ, 2019, 10.1038/s41418-019-0393-7
S3600	Schisandrin B (Sch B) Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety.	Inflammation, 2017, 40(6):1903-1911
S8096	Mirin Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity.	Aging, 2018, 10(4):549-560 DNA Repair, 2018, 70:67-71 Mol Cell Biol, 2017, 37(20)	Wildtype bone marrow-derived macrophages (BMDMs) were incubated with and without the MRN complex inhibitor mirin (administered dose of 100 μM) for 2 hours, then were treated with PM (100 μg/mL) for an additional 24 hours. (A) The relative levels of Cxcl1, Cxcl2 and Ifn-γ mRNA transcripts were determined using quantitative PCR. (B) The protein levels of Cxcl1, Cxcl2 and Ifn-γ in the culture supernatants were measured using ELISA. Data are presented as means ± SEMs across at least 3 independent experiments. p < 0.05; *p < 0.01.
S8666	BAY 1895344 (BAY-1895344) BAY 1895344 is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM.	Nucleic Acids Res, 2019, 10.1093/nar/gkz518
S8375	AZD0156 AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities.	Mol Cell, 2019, 74(3):571-583 Oncogene, 2019, 38(14):2451-2463 Mol Cancer Ther, 2019, 10.1158/1535-7163.MCT-19-0474

Catalog No.	Information	Product Use Citations	Product Validations
S4157	Chloroquine diphosphate Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator.	Sci Adv, 2019, 5(10):eaax7142 EMBO Mol Med, 2019, 11(10):e9930 Theranostics, 2019, 9(26):8392-8408	NCI-H929 EV and miR-137 OE cells were treated with ATM activator Chloroquine Phosphate (CQ), specific ATM inhibitor KU-55933, and ATR inhibitor AZ20 for 12 hr. Immunoblotting showed the expression of p-ATM, p-Chk2, p-BRCA1, p-ATR and p-Chk1.

Catalog No.

Information

Product Use Citations

Product Validations

S4157